This project is aimed at the study of the relationship of benzene metabolism to benzene toxicity. Considerable evidence has demonstrated that toxicity of many hazardous chemicals can be explained by the formation of a reactive intermediate which directly interacts with critical cellular components. Therefore, we plan to study benzene toxicity, as measured by decreases in white blood cell production, while investigating benzene metabolism. We will give mice a series of repeated doses of benzene at several doses and measure the production of benzene metabolites in the urine, benzene metabolites in several organs such as bone marrow and the extent of covalent binding of benzene to proteins or nucleic acids. We will also study the metabolism of benzene in human bone marrow homogenates and in whole cell preparations from rabbit bone marrow. We will seek to determine whether we can find evidence for the production of a toxicologically active metabolite of benzene.